DK169918B1 - Bicykliske sulfonamidderivater - Google Patents

Info

Publication number

DK169918B1

DK169918B1 DK549086A DK549086A DK169918B1 DK 169918 B1 DK169918 B1 DK 169918B1 DK 549086 A DK549086 A DK 549086A DK 549086 A DK549086 A DK 549086A DK 169918 B1 DK169918 B1 DK 169918B1

Authority

DK

Denmark

Prior art keywords

acid

compound

reaction

chloride

mixture

Prior art date

1985-11-18

Links

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• -1 Bicyclic sulfonamide Chemical class 0.000 title claims description 188
• 229940124530 sulfonamide Drugs 0.000 title description 13
• 150000001875 compounds Chemical class 0.000 claims description 182
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
• 229910052739 hydrogen Inorganic materials 0.000 claims description 33
• 239000001257 hydrogen Substances 0.000 claims description 33
• 150000003839 salts Chemical class 0.000 claims description 23
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 125000000217 alkyl group Chemical group 0.000 claims description 20
• HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
• 150000002367 halogens Chemical class 0.000 claims description 9
• 239000001301 oxygen Substances 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
• 239000011593 sulfur Substances 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 125000004432 carbon atom Chemical group C* 0.000 claims description 5
• YURNCBVQZBJDAJ-UHFFFAOYSA-N 2-heptenoic acid Chemical compound CCCCC=CC(O)=O YURNCBVQZBJDAJ-UHFFFAOYSA-N 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• IMPOJXUHCWRAQN-IHWYPQMZSA-N (Z)-2-[3-(benzenesulfonamido)-6-oxabicyclo[3.1.0]hexan-2-yl]hept-5-enoic acid Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC1C(C2OC2C1)C(C(=O)O)CC\C=C/C IMPOJXUHCWRAQN-IHWYPQMZSA-N 0.000 claims description 3
• 125000004450 alkenylene group Chemical group 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• KPSZWAJWFMFMFF-UHFFFAOYSA-N delta-Hexylen-alpha-carbonsaeure Natural products CC=CCCCC(O)=O KPSZWAJWFMFMFF-UHFFFAOYSA-N 0.000 claims description 3
• KPSZWAJWFMFMFF-NSCUHMNNSA-N delta-heptenoic acid Chemical compound C\C=C\CCCC(O)=O KPSZWAJWFMFMFF-NSCUHMNNSA-N 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• VKEQBMCRQDSRET-UHFFFAOYSA-N Methylone Chemical group CNC(C)C(=O)C1=CC=C2OCOC2=C1 VKEQBMCRQDSRET-UHFFFAOYSA-N 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• 125000005037 alkyl phenyl group Chemical group 0.000 claims description 2
• IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical group C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims description 2
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 2
• MJEMIOXXNCZZFK-UHFFFAOYSA-N ethylone Chemical group CCNC(C)C(=O)C1=CC=C2OCOC2=C1 MJEMIOXXNCZZFK-UHFFFAOYSA-N 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 3
• JICKTVCNZLACSE-AEYPFITQSA-N (z)-7-[(1r,3s,4s,5s)-3-(benzenesulfonamido)-6,6-dimethyl-4-bicyclo[3.1.1]heptanyl]hept-5-enoic acid Chemical compound N([C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@]2(C[C@](C1)(C2(C)C)[H])[H])S(=O)(=O)C1=CC=CC=C1 JICKTVCNZLACSE-AEYPFITQSA-N 0.000 claims 1
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
• 125000002619 bicyclic group Chemical group 0.000 claims 1
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 333
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 310
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 234
• 239000000243 solution Substances 0.000 description 220
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 196
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 187
• 239000000203 mixture Substances 0.000 description 186
• 238000006243 chemical reaction Methods 0.000 description 185
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 183
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 180
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 144
• 238000000034 method Methods 0.000 description 136
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 124
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 119
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 119
• 239000002904 solvent Substances 0.000 description 108
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 105
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 96
• 230000002829 reductive effect Effects 0.000 description 92
• 238000005481 NMR spectroscopy Methods 0.000 description 86
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 82
• 150000001299 aldehydes Chemical class 0.000 description 79
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 79
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 78
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 76
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 73
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
• 239000011541 reaction mixture Substances 0.000 description 71
• 239000002585 base Substances 0.000 description 68
• 239000011734 sodium Substances 0.000 description 68
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 66
• 238000004458 analytical method Methods 0.000 description 63
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 62
• 229940086542 triethylamine Drugs 0.000 description 61
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 56
• 238000001816 cooling Methods 0.000 description 53
• 230000008569 process Effects 0.000 description 52
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
• 239000000741 silica gel Substances 0.000 description 45
• 229910002027 silica gel Inorganic materials 0.000 description 45
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 43
• 239000000047 product Substances 0.000 description 43
• 239000002253 acid Substances 0.000 description 41
• 229920006395 saturated elastomer Polymers 0.000 description 39
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 38
• 238000004440 column chromatography Methods 0.000 description 37
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 36
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 36
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 36
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 33
• 239000003054 catalyst Substances 0.000 description 33
• 239000012044 organic layer Substances 0.000 description 33
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 32
• 238000010438 heat treatment Methods 0.000 description 32
• 239000010410 layer Substances 0.000 description 32
• 238000002360 preparation method Methods 0.000 description 31
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 30
• 239000011780 sodium chloride Substances 0.000 description 30
• 229910052938 sodium sulfate Inorganic materials 0.000 description 29
• 235000011152 sodium sulphate Nutrition 0.000 description 29
• 230000015572 biosynthetic process Effects 0.000 description 28
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 28
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
• 239000000460 chlorine Substances 0.000 description 27
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 26
• 150000001412 amines Chemical class 0.000 description 26
• 239000007858 starting material Substances 0.000 description 26
• 150000002148 esters Chemical class 0.000 description 24
• 238000005886 esterification reaction Methods 0.000 description 23
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 23
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 22
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 22
• 125000006239 protecting group Chemical group 0.000 description 22
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 21
• 230000032050 esterification Effects 0.000 description 21
• 229940125782 compound 2 Drugs 0.000 description 20
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 20
• 229910052708 sodium Inorganic materials 0.000 description 20
• 235000017557 sodium bicarbonate Nutrition 0.000 description 19
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 18
• 150000001540 azides Chemical class 0.000 description 18
• 239000003795 chemical substances by application Substances 0.000 description 18
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 18
• 239000012299 nitrogen atmosphere Substances 0.000 description 18
• 238000010992 reflux Methods 0.000 description 18
• 239000012312 sodium hydride Substances 0.000 description 18
• 229910000104 sodium hydride Inorganic materials 0.000 description 18
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 18
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 17
• 238000003786 synthesis reaction Methods 0.000 description 17
• CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 16
• 238000005160 1H NMR spectroscopy Methods 0.000 description 15
• 235000011054 acetic acid Nutrition 0.000 description 15
• 159000000000 sodium salts Chemical class 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 14
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
• 239000003638 chemical reducing agent Substances 0.000 description 14
• 239000012230 colorless oil Substances 0.000 description 14
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
• 235000019341 magnesium sulphate Nutrition 0.000 description 14
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
• 150000002924 oxiranes Chemical class 0.000 description 14
• 238000003756 stirring Methods 0.000 description 14
• 239000000126 substance Substances 0.000 description 14
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 13
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
• 239000012280 lithium aluminium hydride Substances 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 12
• 239000003849 aromatic solvent Substances 0.000 description 12
• USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 12
• 238000005755 formation reaction Methods 0.000 description 12
• 150000004820 halides Chemical class 0.000 description 12
• 239000000543 intermediate Substances 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 11
• 150000008065 acid anhydrides Chemical class 0.000 description 11
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 11
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 11
• 150000002923 oximes Chemical class 0.000 description 11
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 11
• 229910000029 sodium carbonate Inorganic materials 0.000 description 11
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 11
• VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 10
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 10
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 10
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• 229910004298 SiO 2 Inorganic materials 0.000 description 10
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
• 238000007239 Wittig reaction Methods 0.000 description 10
• 229940126214 compound 3 Drugs 0.000 description 10
• 239000013078 crystal Substances 0.000 description 10
• 150000002431 hydrogen Chemical class 0.000 description 10
• 239000007800 oxidant agent Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• 238000000926 separation method Methods 0.000 description 10
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 9
• RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 9
• 229910001863 barium hydroxide Inorganic materials 0.000 description 9
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 9
• 230000007062 hydrolysis Effects 0.000 description 9
• 238000006460 hydrolysis reaction Methods 0.000 description 9
• 239000012948 isocyanate Substances 0.000 description 9
• 150000002513 isocyanates Chemical class 0.000 description 9
• 229910052700 potassium Inorganic materials 0.000 description 9
• 239000011591 potassium Substances 0.000 description 9
• VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 8
• AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 229940125904 compound 1 Drugs 0.000 description 8
• ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
• 230000009467 reduction Effects 0.000 description 8
• 238000006722 reduction reaction Methods 0.000 description 8
• RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 8
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 7
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• SMBZJSVIKJMSFP-UHFFFAOYSA-N trifluoromethyl hypofluorite Chemical compound FOC(F)(F)F SMBZJSVIKJMSFP-UHFFFAOYSA-N 0.000 description 1
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